Highlights

1. Clear MoA.

CD40 is a cell-surface member of the TNF receptors superfamily. CD40 is extensively expressed on APC. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. anti-CD40 IgG subclass binds both activating S(hFcγRIIA) and inhibitory (hFcγRIIB) IgG receptors. Anti-CD40 can only have anti-tumor effects when it selectively binds to FcyRⅡB.

2. Excellent preclinical efficacy:

(1) Cross with human and rhesus monkeys, not with mouse/ rats.

(2) No immunotoxicity: no ADCC activity, lower CDC activity than APX004M.

(3) Higher tumor-killing activity and higher immune memory effect than RO7009789 and APX005M in vivo.

(4) Excellent safety: MTD= 30 mg/kg in rhesus monkeys; Plasma cytokine concentrations (IFNγ, TNFα, IL6, IL1β, IL2, IL4) were not abnormally increased after mAb administration.

3. Excellent PhaseⅠclinical result:

(1) No DLTs or SAEs observed in the dosages tested (0.01mg/kg through 0.1mg/kg).

(2) One patient with metastatic melanoma treated with a low dose (0.03 mg/kg) of the CD40 mAb achieved SD.

4. Good market potential:

It is estimated that the number of new pancreatic cancer patients worldwide will reach 486,300 in 2028, and the pancreatic cancer drug market will reach US$4.1 billion.

Research progress：

1) Completed preclinical development

2) Phase I clinical trials were initiated to evaluate the safety, tolerability, pharmacokinetics and efficacy of candidate antibodies for advanced malignancies.